Example 15 of Patent Literature 1 describes (2S)-5-amino-2-{[1-(trans-4-methylcyclohexyl)-1H-imidazol-4-yl]methyl}valeric acid having an excellent TAFIa enzyme inhibitory activity and a method for producing the same.
Specifically, ethyl 1-(trans-4-methylcyclohexyl)-1H-imidazole-4-carboxylate is used as a starting material, and reduction of an ester to an alcohol, oxidation of the alcohol to an aldehyde, Knoevenagel condensation and olefin reduction are performed to synthesize a racemate, methyl 5-[(tert-butoxycarbonyl)amino]-2-{[1-(trans-4-methylcyclohexyl)-1H-imidazol-4-yl]methyl}valerate. Thereafter, an enantiomer is separated from the compound using optically active column chromatography, the ester thereof is then hydrolyzed, and the protective group for the amino group is then removed, so as to produce an optically active form, (2S)-5-amino-2-{[1-(trans-4-methylcyclohexyl)-1H-imidazol-4-yl]methyl}valeric acid.
However, in the method of separating the racemate using optically active column chromatography, the enantiomer having a steric structure opposite to that intended is wasted, and such separation operations are complicated. Thus, this method is not industrially preferable.